engleski

Synthesis of New Acyclic Pyrimidine Nucleoside Analogues and Preliminary of Their Cytotoxic and Genotoxic Effects In Vitro

Nucleoside analogues represent an important class of compounds of wide application range in antiviral and antitumor therapy. A regular procedure in early phases of new drugs development includes assessment of cytotoxicity and genotoxicity (mutagenicity). Here we report the synthesis of two novel C-5 hydroxypropyl pyrimidine nucleosides bearing side chains like those present in drugs already used in therapy (penciclovir and cidofovir). To confirm structures of the newly synthesized compounds FT-IR, HPLC-MS and NMR spectroscopy in solution were used. New hydroxypropyl pyrimidine nucleosides were N-3-(2, 3-dihydroxypropyl)-5- (3-hydroxypropyl)pyrimidine-2, 4-dione and N-3- (4-hydroxy-3-(hydroxymethyl)butyl)-5-(3- hydroxypropyl)pyrimidine-2, 4-dione.Along with two new, we have also tested three previously synthesized nucleosides for genotoxicity and cytotoxicity using cytokinesis-block micronucleus (CBMN) assay on human peripheral blood lymphocytes. Not many studies so far used the same cell model and CBMN assay to determine cyto-/genotoxicity of pyrimidine nucleosides. Results of CBMN assay did not indicate statistically significant cyto-/genotoxicity towards human peripheral blood lymphocytes. Since preliminary testing did not suggest significant genotoxic or cytotoxic potency of novel hydroxypropyl pyrimidine nucleosides, they are excellent candidates for further biological evaluation, primarily as antiviral agents.

Pyrimidine analogues ; Acyclic nucleosides ; CBMN assay ; Genotoxicity ; Cytotoxicity

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